Bone Morphogenetic Protein functions as a context-dependent angiogenic cue in vertebrates

Wiley, David M.; Jin, Suk‐Won

doi:10.1016/j.semcdb.2011.10.005

Cited by 31 publications

(41 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Genetic mutants of BMP signaling pathway exhibited a dorsalized axial pattern and pharmacological inhibitors of BMP signaling-inhibited sprouting angiogenesis along the caudal vein plexus (CVP) of the axial vein, a ventral structure in zebrafish. 36 Conversely, activation of BMP signaling (by overexpression of an activated BMP type II receptor) induced ectopic sprouts along the axial vein. 37 To examine the effect of miR-26a on BMP-dependent angiogenesis, we overexpressed miR-26a in zebrafish flk:eGFP embryos (Online Figure V) that severely impaired the development of the CVP of the axial vein, a BMP-responsive process, 37 by 48 hours after fertilization (Figure 5A).…”

Section: Resultsmentioning

confidence: 99%

MicroRNA-26a Regulates Pathological and Physiological Angiogenesis by Targeting BMP/SMAD1 Signaling

Icli

Wara

Moslehi

et al. 2013

Circulation Research

192

161

View full text Add to dashboard Cite

Rationale The rapid induction and orchestration of new blood vessels are critical for tissue repair in response to injury, such as myocardial infarction, and for physiological angiogenic responses, such as embryonic development and exercise. Objective We aimed to identify and characterize microRNAs (miR) that regulate pathological and physiological angiogenesis. Methods and Results We show that miR-26a regulates pathological and physiological angiogenesis by targeting endothelial cell (EC) bone morphogenic protein/SMAD1 signaling in vitro and in vivo. MiR-26a expression is increased in a model of acute myocardial infarction in mice and in human subjects with acute coronary syndromes. Ectopic expression of miR-26a markedly induced EC cycle arrest and inhibited EC migration, sprouting angiogenesis, and network tube formation in matrigel, whereas blockade of miR-26a had the opposite effects. Mechanistic studies demonstrate that miR-26a inhibits the bone morphogenic protein/SMAD1 signaling pathway in ECs by binding to the SMAD1 3′-untranslated region, an effect that decreased expression of Id1 and increased p21WAF/CIP and p27. In zebrafish, miR-26a overexpression inhibited formation of the caudal vein plexus, a bone morphogenic protein-responsive process, an effect rescued by ectopic SMAD1 expression. In mice, miR-26a overexpression inhibited EC SMAD1 expression and exercise-induced angiogenesis. Furthermore, systemic intravenous administration of an miR-26a inhibitor, locked nucleic acid-anti–miR-26a, increased SMAD1 expression and rapidly induced robust angiogenesis within 2 days, an effect associated with reduced myocardial infarct size and improved heart function. Conclusions These findings establish miR-26a as a regulator of bone morphogenic protein/SMAD1-mediated EC angiogenic responses, and that manipulating miR-26a expression could provide a new target for rapid angiogenic therapy in ischemic disease states.

show abstract

Section: Resultsmentioning

confidence: 99%

MicroRNA-26a Regulates Pathological and Physiological Angiogenesis by Targeting BMP/SMAD1 Signaling

Icli

Wara

Moslehi

et al. 2013

Circulation Research

192

161

View full text Add to dashboard Cite

show abstract

“…The BMP pathway has many known roles in endothelial cells, where it can promote endothelial cell migration, proliferation, and apoptosis (Wiley and Jin, 2011). Some of these specific roles have been attributed to individual BMPs and particular intracellular pathways.…”

Section: Discussionmentioning

confidence: 99%

“…The effects of the BMPs on endothelial cell function are highly context dependent, with a single BMP being capable of signaling through multiple intracellular pathways. BMPs can stimulate cell migration, angiogenesis, apoptosis, and proliferation in some settings yet inhibit proliferation and apoptosis in others (Bobik, 2006; Wiley and Jin, 2011). The BMP signaling pathway is complex and regulated at many different levels.…”

Section: Introductionmentioning

confidence: 99%

BMPER-induced BMP signaling promotes coronary artery remodeling

Dyer

Moser

et al. 2014

Developmental Biology

View full text Add to dashboard Cite

Summary The connection of the coronary vasculature to the aorta is one of the last essential steps of cardiac development. However, little is known about the signaling events that promote normal coronary artery formation. The bone morphogenetic protein (BMP) signaling pathway regulates multiple aspects of endothelial cell biology but has not been specifically implicated in coronary vascular development. BMP signaling is tightly regulated by numerous factors, including BMP-binding endothelial cell precursor-derived regulator (BMPER), which can both promote and repress BMP signaling activity. In the embryonic heart, BMPER expression is limited to the endothelial cells and the endothelial-derived cushions, suggesting that BMPER may play a role in coronary vascular development. Histological analysis of BMPER−/− embryos at early embryonic stages demonstrates that commencement of coronary plexus differentiation is normal and that endothelial apoptosis and cell proliferation are unaffected in BMPER−/− embryos compared with wild-type embryos. However, analysis between embryonic days 15.5-17.5 reveals that, in BMPER−/− embryos, coronary arteries are either atretic or connected distal to the semilunar valves. In vitro tubulogenesis assays indicate that isolated BMPER−/− endothelial cells have impaired tube formation and migratory ability compared with wild-type endothelial cells, suggesting that these defects may lead to the observed coronary artery anomalies seen in BMPER−/− embryos. Additionally, recombinant BMPER promotes wild-type ventricular endothelial migration in a dose-dependent manner, with a low concentration promoting and high concentrations inhibiting migration. Together, these results indicate that BMPER-regulated BMP signaling is critical for coronary plexus remodeling and normal coronary artery development.

show abstract

“…Proangiogenic and proinflammatory effects of Bmp2 have been studied in detail in cultured ECs. [4][5][6] Few studies, however, have addressed potential angiocrine functions of Bmp2 in vivo. [7][8][9] Recently, 2 nonredundant signaling pathways have been proposed that control hepatic hepcidin expression and iron homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Angiocrine Bmp2 signaling in murine liver controls normal iron homeostasis

Koch¹,

Olsavszky²,

Ulbrich³

et al. 2017

Blood

131

129

View full text Add to dashboard Cite

Key Points• Angiocrine Bmp2 signaling in the liver controls tissue and serum iron concentrations via regulation of hepcidin expression in hepatocytes.• Liver-specific angiocrine signaling is essential for the metabolic homeostasis of the whole organism.Microvascular endothelial cells (ECs) display a high degree of phenotypic and functional heterogeneity among different organs. Organ-specific ECs control their tissue microenvironment by angiocrine factors in health and disease. Liver sinusoidal endothelial cells (LSECs) are uniquely differentiated to fulfill important organ-specific functions in development, under homeostatic conditions, and in regeneration and liver pathology. Recently, Bmp2 has been identified by us as an organ-specific angiokine derived from LSECs. To study angiocrine Bmp2 signaling in the liver, we conditionally deleted Bmp2 in LSECs using EC subtype-specific Stab2-Cre mice. Genetic inactivation of hepatic angiocrine Bmp2 signaling in Stab2-Cre;Bmp2 fl/fl (Bmp2 LSECKO ) mice caused massive iron overload in the liver and increased serum iron levels and iron deposition in several organs similar to classic hereditary hemochromatosis. Iron overload was mediated by decreased hepatic expression of hepcidin, a key regulator of iron homeostasis. Thus, angiocrine Bmp2 signaling within the hepatic vascular niche represents a constitutive pathway indispensable for iron homeostasis in vivo that is nonredundant with Bmp6. Notably, we demonstrate that organ-specific angiocrine signaling is essential not only for the homeostasis of the respective organ but also for the homeostasis of the whole organism. (Blood. 2017;129(4):415-419)

show abstract

Bone Morphogenetic Protein functions as a context-dependent angiogenic cue in vertebrates

Cited by 31 publications

References 93 publications

MicroRNA-26a Regulates Pathological and Physiological Angiogenesis by Targeting BMP/SMAD1 Signaling

MicroRNA-26a Regulates Pathological and Physiological Angiogenesis by Targeting BMP/SMAD1 Signaling

BMPER-induced BMP signaling promotes coronary artery remodeling

Angiocrine Bmp2 signaling in murine liver controls normal iron homeostasis

Contact Info

Product

Resources

About